Steroids-Based Screening for Primary Aldosteronism

Overview

This prospective, single-center observational study aims to evaluate whether a steroid-based screening method can more accurately identify Primary Aldosteronism (PA) in hypertensive patients who remain on their usual antihypertensive medications, compared with the conventional aldosterone-to-renin ratio (ARR). PA is a common, potentially curable subtype of secondary hypertension that carries increased cardiovascular risk when undiagnosed or untreated. However, current screening protocols recommend "medication washout" or switching to minimally interfering drugs, which may pose safety concerns and add complexity. In this study, approximately 406 participants (ages 18-75) with diagnosed hypertension and on at least one interfering antihypertensive drug (such as ACE inhibitors, ARBs, beta-blockers, diuretics, or calcium channel blockers) will be enrolled at the Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University. Each participant will undergo two rounds of blood sampling-first while continuing their usual antihypertensive regimen (the "on-medication" state) and second following a standardized washout/switch period (the "standard state"), if medically feasible. At both stages, levels of plasma aldosterone, renin, and a broad panel of adrenal steroid hormones will be measured by liquid chromatography-tandem mass spectrometry. By comparing diagnostic performance (e.g., sensitivity, specificity, and area under the receiver operating characteristic curve) of the steroid-based screening versus the ARR, the study seeks to determine whether steroid profiling improves accuracy under real-world treatment conditions. Findings may help refine PA screening strategies, reduce the need for extensive medication adjustments, and contribute to better clinical management of hypertension.

Interventions

• Diagnostic test Steroid-Based Screening (LC-MS/MS)
  This diagnostic intervention is a liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based steroid profiling assay. It measures a panel of 18 adrenal steroid hormones (e.g., aldosterone, 18-hydroxycortisol, 18-oxocortisol, corticosterone) from plasma samples. In this study, it is used to screen for Primary Aldosteronism (PA) while patients remain on their usual antihypertensive medications. By comparing these steroid profiles against standard aldosterone-renin measurements, the method aim

Primary outcome measures

• Diagnostic Accuracy of Steroid-Based Screening vs. ARR for Primary Aldosteronism in Patients on Antihypertensive Medications [Time frame: From baseline screening while on medication to completion of confirmatory testing, approximately 4-8 weeks.]

Eligibility criteria

Inclusion criteria

• Aged 18-75 years, with no sex restriction.
• Diagnosed with hypertension, defined as a systolic blood pressure ≥140 mmHg and/or a diastolic blood pressure ≥90 mmHg measured on at least two different days.
• Currently receiving at least one antihypertensive medication that interferes with aldosterone or renin (ACEI/ARB, β-blockers, dihydropyridine CCBs, or diuretics including MRA) for ≥4 consecutive weeks.
• Fully informed about the study procedures and risks, and willing to participate by signing a written informed consent form.

Exclusion criteria

• Confirmed secondary hypertension of other etiologies (e.g., renovascular hypertension, renal artery stenosis, reninoma, pheochromocytoma, Cushing's syndrome, Liddle syndrome), excluding obstructive sleep apnea.
• Severe cardiac, hepatic, or renal impairment or serious infections, including but not limited to New York Heart Association (NYHA) Class III-IV heart failure, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels exceeding 2.5 times the upper limit of normal, estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m², or severe infections (e.g., diabetic foot, sepsis, pneumonia, refractory infections).
• History of major cardiovascular or cerebrovascular events within the past 3 months.
• Pregnant or breastfeeding women.
• Currently using medications (other than the listed antihypertensives) that may affect aldosterone or renin secretion, including but not limited to sex hormones (e.g., oral contraceptives, estrogen replacement therapy), glucocorticoids (e.g., prednisone, dexamethasone), nonsteroidal anti-inflammatory drugs (NSAIDs, e.g., aspirin, ibuprofen), or antipsychotics (e.g., chlorpromazine, olanzapine).
• Individuals lacking or having restricted capacity for independent decision-making or action.
• History of psychiatric disorders.
• Poor compliance likely to compromise study completion.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

China · 1 center

• The First Affiliated Hospital of Chongqing Medical University — Chongqing

Publications

• Constantinescu G, Gruber S, Fuld S, Peitzsch M, Schulze M, Remde H, Kurzinger L, Yang J, Yen T, Williams TA, Muller L, Reincke M, Lenders JWM, Beuschlein F, Pamporaki C, Eisenhofer GF. Steroidomics-Based Screening for Primary Aldosteronism: Impact of antihypertensive Drugs. Hypertension. 2024 Oct;81(10):2060-2071. doi: 10.1161/HYPERTENSIONAHA.124.23029. Epub 2024 Jul 31. PMID 39082132
• Eisenhofer G, Duran C, Cannistraci CV, Peitzsch M, Williams TA, Riester A, Burrello J, Buffolo F, Prejbisz A, Beuschlein F, Januszewicz A, Mulatero P, Lenders JWM, Reincke M. Use of Steroid Profiling Combined With Machine Learning for Identification and Subtype Classification in Primary Aldosteronism. JAMA Netw Open. 2020 Sep 1;3(9):e2016209. doi: 10.1001/jamanetworkopen.2020.16209. PMID 32990741
• Li X, Liang J, Hu J, Ma L, Yang J, Zhang A, Jing Y, Song Y, Yang Y, Feng Z, Du Z, Wang Y, Luo T, He W, Shu X, Yang S, Li Q; Chongqing Primary Aldosteronism Study (CONPASS) Group. Screening for primary aldosteronism on and off interfering medications. Endocrine. 2024 Jan;83(1):178-187. doi: 10.1007/s12020-023-03520-6. Epub 2023 Oct 5. PMID 37796417
• Liu X, Hao S, Bian J, Lou Y, Zhang H, Wu H, Cai J, Ma W. Performance of Aldosterone-to-renin Ratio Before Washout of Antihypertensive Drugs in Screening of Primary Aldosteronism. J Clin Endocrinol Metab. 2024 Nov 18;109(12):e2302-e2308. doi: 10.1210/clinem/dgae094. PMID 38381080
• Fischer E, Beuschlein F, Bidlingmaier M, Reincke M. Commentary on the Endocrine Society Practice Guidelines: Consequences of adjustment of antihypertensive medication in screening of primary aldosteronism. Rev Endocr Metab Disord. 2011 Mar;12(1):43-8. doi: 10.1007/s11154-011-9163-7. PMID 21331645
• Mulatero P, Monticone S, Deinum J, Amar L, Prejbisz A, Zennaro MC, Beuschlein F, Rossi GP, Nishikawa T, Morganti A, Seccia TM, Lin YH, Fallo F, Widimsky J. Genetics, prevalence, screening and confirmation of primary aldosteronism: a position statement and consensus of the Working Group on Endocrine Hypertension of The European Society of Hypertension. J Hypertens. 2020 Oct;38(10):1919-1928. doi: 1 PMID 32890264
• Griffin TP, Browne GA, Wall D, Dennedy MC, O'Shea PM. A cross-sectional study of the effects of beta-blocker therapy on the interpretation of the aldosterone/renin ratio: can dosing regimen predict effect? J Hypertens. 2016 Feb;34(2):307-15. doi: 10.1097/HJH.0000000000000775. PMID 26867057
• Browne GA, Griffin TP, O'Shea PM, Dennedy MC. beta-Blocker withdrawal is preferable for accurate interpretation of the aldosterone-renin ratio in chronically treated hypertension. Clin Endocrinol (Oxf). 2016 Mar;84(3):325-31. doi: 10.1111/cen.12882. Epub 2015 Sep 22. PMID 26300226

Identifiers

NCT: NCT06941116 · SAFE Study

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗